A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Test the Safety and Efficacy of Lipitor (Atorvastatin) in Reducing the Progression of Carotid IMT in Early Childhood SLE
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 221
- 试验地点
- 1
- 主要终点
- Change in Mean-Mean Common Carotid IMT (CIMT)
研究概览
简要总结
The purpose of this study is:
- To assess the efficacy of a lipid-lowering agent (atorvastatin) on the development of atherosclerosis that predisposes children with SLE to cardiovascular events in adulthood.
- To assess the safety of intermediate-term (36 months) treatment of children and young adults with atorvastatin.
- To further characterize the course of SLE in children and young adults, by establishing a cohort of pediatric SLE patients to be followed prospectively.
- To establish a mechanism for conducting clinical trials in rare pediatric rheumatic diseases using the Children's Arthritis and Rheumatology Research Alliance (CARRA).
详细描述
Children and adolescents with SLE represent 15% of all SLE patients. Children with SLE suffer high morbidity that affects many organ systems, reduces their quality of life, and shortens their lifespan. As more children with SLE survive into adulthood, atherosclerotic cardiovascular disease has emerged as a major concern. SLE is a significant risk factor for myocardial infarction and death in young premenopausal women with SLE, even after controlling for traditional cardiovascular risk factors. Acceleration of atherogenesis in SLE most likely reflects SLE-associated vascular immune and inflammatory changes.
Although limited, the data on cardiovascular and lipid abnormalities in children with SLE implicate atherosclerosis as an important cause of long-term morbidity and mortality. The 3-hydroxy-3-methlglutaryl-coenzyme A (HMG CoA) reductase inhibitors, or statins, reduce mortality and morbidity from atherosclerosis in adults and have intrinsic anti-inflammatory and immune modulatory properties. These anti-inflammatory and immune modulatory activities may have particular benefit in the prevention and treatment of atherosclerosis in SLE. This trial will evaluate atorvastatin in children with SLE in the largest cohort of pediatric SLE patients ever studied prospectively.
Children in this study will be randomized to receive either atorvastatin or a placebo. All children will be followed for 3 years, during which they will have 15 study visits. Study visits will generally last 2 hours and will include medical interview, medication review and pill count, physical examination, and blood and urine tests. Cardiovascular-specific outcome measures will include assessments of high sensitivity CRP; fasting lipid profile; homocysteine level; apolipoprotein A, B1, and Lp(a); carotid intima media thickness (IMT); and tensor diffusion/MRI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 10 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets American College of Rheumatology (ACR) revised diagnostic guidelines for SLE
- •Weight of 25 kg (55 lbs) or more
- •Outpatient
- •Ability to complete self-report questionnaires in either English or Spanish
- •Willingness to comply with recommended diet
- •Acceptable methods of contraception
排除标准
- •Drug-induced lupus
- •Liver disease (ALT or aspartate aminotransferase greater than 2 X normal value)
- •Myositis (CK greater than 3 X normal value)
- •Inability to obtain adequate-quality IMT images
- •Current use of oral or parenteral tacrolimus or cyclosporine
- •Dialysis or serum creatinine reater than 2.5 mg/dL
- •Active nephrotic syndrome (urinary protein greater than 3 g/24 h and serum albumin less than 2.3 g/dl)
- •Total cholesterol greater than 350 mg/dL
- •Familial hypercholesterolemia
- •Pregnant or breastfeeding
- •Use of estrogen-containing contraceptives (e.g., Lo-Ovral)
- •Unable to adhere to study regimen
- •Life-threatening non-SLE illness that would interfere with ability to complete the study
- •Current drug or alcohol abuse
- •Anticipated poor compliance
- •Participation in another drug intervention study within 30 days of study enrollment
研究组 & 干预措施
1
Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi\]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus atorvastatin at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd atorvastatin for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.
干预措施: Atorvastatin (Drug)
2
Patients will be treated with dietary intervention (AHA Therapeutic Lifestyle Changes [TLC] diet, [http://www.nhlbi.nih.gov/cgi-bin/chd/step2intro.cgi\]), cardiovascular risk factor reduction counseling, hydroxychloroquine, low-dose aspirin, a multivitamin containing folate, plus placebo at 10 mg or 20 mg depending on the patient's weight. Patients weighing more than 50 kg will receive 10 mg qd placebo for the first month, which will be increased to 20 mg qd at the Day 30 visit and continue through month 36. Participants weighing less than 50kg will receive a maximum of 10 mg po qd for 36 months.
干预措施: Placebo atorvastatin (Drug)
结局指标
主要结局
Change in Mean-Mean Common Carotid IMT (CIMT)
时间窗: Change from baseline to 36 months
For the common carotid arterial segment, mean CIMT values were averaged across angles by side and wall to produce 4 summary variables (right common near wall mean, right common far wall mean, left common near wall mean and left common far wall mean). These summary variables were then averaged to estimate a single mean-mean common CIMT for each participant visit.
次要结局
- Change in Mean-Max CIMT(Change from baseline to 36 months)
- Change in Mean-Mean CIMT(Change from baseline to 36 months)
- Change in Mean-Max Common CIMT(Change from baseline to 36 months)
- Change in Mean-Max Internal CIMT(Change from baseline to 36 months)
- Change in Mean-Mean Internal CIMT(Change from baseline to 36 months)
- Change in Mean-Max Bifurcation CIMT(Change from baseline to 36 months)
- Change in Mean-Mean Bifurcation CIMT(Change from baseline to 36 months)
- Change in Mean-Max Far Wall CIMT(Change from baseline to 36 months)
- Change in Mean-Mean Far Wall CIMT(Change from baseline to 36 months)
- Change in Mean-Max Near Wall CIMT(Change from baseline to 36 months)
- Change in Mean-Mean Near Wall CIMT(Change from baseline to 36 months)
- Change in Natural Log of mg/L for hsCRP(Change from baseline to 36 months)
- Change in Total Cholesterol(Change from baseline to 36 months)
- Change in HDL Cholesterol(Change from baseline to 36 months)
- Change in LDL Cholesterol(Change from baseline to 36 months)
- Change in Triglycerides(Change from baseline to 36 months)
- Change in Lipoprotein A(Change from baseline to 36 months)
- Change in Homocysteine(Change from baseline to 36 months)
研究者
Laura Schanberg
Associate Director, Professor
Duke University